Medical treatment often requires the administration of a therapeutic agent (e.g., medicament, drugs, etc.) to a particular part of a patient's body. As patients live longer and are diagnosed with chronic and/or debilitating ailments, the likely result will be an increased need to place even more protein therapeutics, small-molecule drugs, and other medications into targeted areas throughout the patient's body. Some maladies, however, are difficult to treat with currently available therapies and/or require administration of drugs to anatomical regions to which access is difficult to achieve.
A patient's eye is a prime example of a difficult-to-reach anatomical region, and many vision-threatening diseases, including retinitis pigmentosa, age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, are difficult to treat with many of the currently available therapies. For example, oral medications can have systemic side effects; topical applications may sting and engender poor patient compliance; injections generally require a medical visit, can be painful, and risk infection; and sustained-release implants must typically be removed after their supply is exhausted (and generally offer limited ability to change the dose in response to the clinical picture).
Another example is cancer, such as breast cancer or meningiomas, where large doses of highly toxic chemotherapies, such as rapamycin, bevacizumab (e.g., Avastin), or irinotecan (CPT-11), are typically administered to the patient intravenously, which may result in numerous undesired side effects outside the targeted area. Yet another example is drug delivery to the knee, where drugs often have difficulty penetrating the avascular cartilage tissue for diseases such as osteoarthritis.
Implantable drug-delivery devices, which may have a refillable drug reservoir, a cannula for delivering the drug, etc., generally allow for controlled delivery of pharmaceutical solutions to a specified target. The devices may be either passively controlled or actively controlled. In a passively-controlled device, drug is pumped out when, for example, a finger is pressed on the drug reservoir. In an actively-controlled device, drug may be pumped out automatically, for example at regular intervals or continuously over time. In either case, as drug within the drug reservoir depletes, the physician can refill the reservoir with, for example, a syringe, while leaving the device implanted within the patient's body. This approach can minimize the surgical incision needed for implantation and typically avoids future or repeated invasive surgery or procedures.
A variety of challenges, however, are associated with refillable drug-delivery devices. One limitation of conventional drug-delivery devices is that they are typically unable to dynamically respond to changes inside the device (e.g., failures, blockages, etc.) or to changes in the drug-delivery target. For example, tissue growth at the outlet of an implanted device (e.g., at the outlet of the cannula) may create a fluidic restriction. In this case, passive and active drug-delivery devices with no feedback control would likely not deliver the desired flow rate or dose of the drug. Similarly, without feedback, the desired flow rate or dose may not be delivered in the presence of temperature fluctuations, where there are variations in the drug-delivery device due to varying manufacturing processes, where different drug formulations are administered, etc.
A need exists, therefore, for improved implantable drug-delivery devices.